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Pulmonary function testing (PFT) allows for quantitative analysis of lung function. However, as a result of the coronavirus disease 2019 (COVID-19) pandemic, a majority of international medical societies have postponed PFTs in an effort to mitigate disease transmission, complicating the continuity of care in high-risk patients diagnosed with COVID-19 or preexisting lung pathologies. Here, we describe the development of a non-contact wearable pulmonary sensor for pulmonary waveform analysis, pulmonary volume quantification, and crude thoracic imaging using the eddy current (EC) phenomenon. Statistical regression analysis is performed to confirm the predictive validity of the sensor, and all data are continuously and digitally stored with a sampling rate of 6,660 samples/second. Wearable pulmonary function sensors may facilitate rapid point-of-care monitoring for high-risk individuals, especially during the COVID-19 pandemic, and easily interface with patient hospital records or telehealth services., (© 2021. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson's correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = -0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis., (© 2021. The Author(s).)

Existing paradigms for stroke diagnosis typically involve computed tomography (CT) imaging to classify ischemic versus hemorrhagic stroke variants, as treatment for these subtypes varies widely. Delays in diagnosis and transport of unstable patients may worsen neurological status. To address these issues, we describe the development of a rapid, portable, and accurate eddy current damping (ECD) stroke sensor. Copper wire was wound to create large (11.4 cm), medium (4.5 cm), and small (1.5 cm) solenoid coils with varying diameters, with each connected to an inductance-to-digital converter. Eight human participants were recruited between December 15, 2019 and March 15, 2020, including two hemorrhagic stroke, two ischemic stroke, one subarachnoid hemorrhage, and three control participants. Observers were blinded to lesion type and location. A head cap with 8 horizontal scanning paths was placed on the patient. The sensor was tangentially rotated across each row on the patient's head circumferentially. Consent, positioning, and scanning with the sensor took roughly 15 min from start to end for each participant and all scanning took place at the patient bedside. The ECD sensor accurately classified and imaged each of the varying stroke types in each patient. The sensor additionally detected ischemic and hemorrhagic lesions located deep inside the brain, and its range is selectively tunable during sensor design and fabrication.

Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H 2 O 2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H 2 O 2 -induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect.

Obesity increases the risk of hepatocellular carcinoma (HCC), but precise identification and characterization of druggable oncogenic pathways that contribute to the progression of NAFLD to HCC, and hence to the increased incidence and aggressiveness of HCC in obese individuals is lacking. In this regard, we demonstrate that the Indian Hedgehog (Ihh) signaling pathway is upregulated in the fatty livers of mice consuming a high fat diet, and furthermore sustained in HCC tumors specifically within the context of a NAFLD microenvironment. Using a diet-induced mouse model of HCC wherein only obese mice develop HCC, targeted ablation of hepatocyte-secreted Ihh results in a decreased tumor burden and lower grade tumors. Ihh activation regulates the transdifferentiation of ciliated stellate cells and proliferation of Epcam + ductal cells to promote fibrosis. Mechanistically, increased expression of hitherto uncharacterized effectors of Hh pathway, namely Myc and Tgf-β2 is critical to the observed physiology. This pro-tumorigenic response is driven by increased expression of Wnt5a to effect a poorly-differentiated and invasive tumor phenotype. Wnt5a secreted from activated stellate cells act on Ror2-expressing hepatocytes. We further demonstrate that Wnt5a expression is also elevated in poorly-differentiated HCC cells, suggesting that these ligands are also able to function in an autocrine positive feedback manner to sustain poorly-differentiated tumors. Taken together, our study provides a mechanistic understanding for how Ihh signaling promotes HCC tumorigenesis specifically in obese mice. We propose that therapeutic targeting of the Hh pathway offers benefit for patients with dietary / NAFLD-driven steatotic HCC.

Blood viscosity provides the rheological basis to elucidate shear stress underlying developmental cardiac mechanics and physiology. Zebrafish is a high throughput model for developmental biology, forward-genetics, and drug discovery. The micro-scale posed an experimental challenge to measure blood viscosity. To address this challenge, a microfluidic viscometer driven by surface tension was developed to reduce the sample volume required (3μL) for rapid (<2 min) and continuous viscosity measurement. By fitting the power-law fluid model to the travel distance of blood through the micro-channel as a function of time and channel configuration, the experimentally acquired blood viscosity was compared with a vacuum-driven capillary viscometer at high shear rates (>500 s -1 ), at which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a Newtonian fluid. The measured values of whole blood from the micro-channel (4.17cP) and the vacuum method (4.22cP) at 500 s -1 were closely correlated at 27 °C. A calibration curve was established for viscosity as a function of hematocrits to predict a rise and fall in viscosity during embryonic development. Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity during development.

The integrated stress response (ISR) is a homeostatic mechanism by which eukaryotic cells sense and respond to stress-inducing signals, such as amino acid starvation. General controlled non-repressed (GCN2) kinase is a key orchestrator of the ISR, and modulates protein synthesis in response to amino acid starvation. Here we demonstrate in mice that GCN2 controls intestinal inflammation by suppressing inflammasome activation. Enhanced activation of ISR was observed in intestinal antigen presenting cells (APCs) and epithelial cells during amino acid starvation, or intestinal inflammation. Genetic deletion of Gcn2 (also known as Eif2ka4) in CD11c(+) APCs or intestinal epithelial cells resulted in enhanced intestinal inflammation and T helper 17 cell (TH17) responses, owing to enhanced inflammasome activation and interleukin (IL)-1β production. This was caused by reduced autophagy in Gcn2(-/-) intestinal APCs and epithelial cells, leading to increased reactive oxygen species (ROS), a potent activator of inflammasomes. Thus, conditional ablation of Atg5 or Atg7 in intestinal APCs resulted in enhanced ROS and TH17 responses. Furthermore, in vivo blockade of ROS and IL-1β resulted in inhibition of TH17 responses and reduced inflammation in Gcn2(-/-) mice. Importantly, acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2. These results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2.

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 10(3)), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.